Enzyme induction alcohol

Taken with alcohol they potentiate the sedative effects and impairment of psychomotor performance. Hepatic enzyme induction by barbiturates or nicotine may reduce plasma levels. Cimetidine may increase levels by enzyme inhi bition. Some antipsychotic drugs may compete for similar metabolic pathways. 

Chronic alcoholism results in enzyme induction. Acute alcoholic intoxication tends to inhibit drug metabolism (whether person is alcoholic or not). Severe alcohol-induced hepatic dysfunction may inhibit ability to metabolize drugs. Disulfiram-like reaction in the presence of certain drugs. Additive central nervous system depression with other central nervous system depressants. 

Most sulfonylureas are at least partly metabolized in the liver (SEDA-9, 709) (57), and hence liver insufficiency, liver disease, and liver enzyme inhibition (alcohol) or induction (drugs) can alter the half-life of the drug and its duration of action. 

Gamma-glutamyl transpeptidase (GGT, y-GT) Biliary epithelia, hepatocytes 0-50 lU/L Raised in many forms of liver disease and in enzyme induction, e.g. alcohol or certain medicines... 

Increased metabolism as a result of enzyme induction (see p. 113) also leads to tolerance, as experience shows with alcohol, taken regularly as opposed to sporadically. There is commonly crosstolerance between drugs of similar structure. 

Variability in response to drugs is increased. Enzyme induction caused by heavy alcohol drinking or heavy smoking may be an... 

Chronic alcohol ingestion causing enzyme induction is a likely explanation of the tolerance... 

Drug metabolism may also be increased by hepatic enzyme induction from insecticide acciunu-lation, e.g. dicophane (DDT) and from alcohol and the tobacco habit, e.g. smokers require a higher dose of theophylline. 

Effects on sexual function. Nothing really new has been said since William Shakespeare wrote that alcohol provokes the desire, but it takes away the performance. Performance in other forms of athletics is also impaired. Prolonged substantial consumption lowers plasma testosterone concentration at least partly as a result of hepatic enzyme induction ... 

Tolerance to alcohol can be acquired and the point has been made that it costs the regular heavy drinker 2.5 times as much to get visibly drunk as it would cost the average abstainer. This is probably due both to enzyme induction and to adaptation of the central nervous system. 

Oral anticoagulants. Control may be disturbed by alcohol inhibiting hepahc metabohsm acutely, or enhancing it by enzyme induction moderate drinking is unlikely to cause trouble. 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

Thus, the importance of enzyme induction is that it may alter the toxicity of a foreign compound. This can have important clinical consequences and underlie drug interactions. Thus, the antitubercular drug rifampicin is thought to increase the hepatotoxicity of the drug isoniazid, and alcohol may increase susceptibility to the hepatotoxicity of... 

Examples of drugs that are well known to cause enzyme induction are carbamazepine, phenytoin (both antiepileptics) and alcohol. 

Enzyme induction Drug induces increased activity of enzymes Alcohol induces enzymes that metabolize warfarin... 

Measurement of y glutamyl transpeptidase can give an indication of hepatocellular enzyme induction due to drugs or alcohol. 

Information is limited, but the interaction between doxycycline and alcohol appears to be established and of clinical significance in alcoholics but not in non-alcoholic individuals. One possible solution to the problem of enzyme induction is to give alcoholic subjects double the dose of doxycy-cline. Alternatively tetracycline may be a suitable non-interacting alternative. There is nothing to suggest that moderate or even occasional heavy drinking has a clinically relevant effect on any of the tetracyclines in non-alcoholic subjects. 

Both alcohol and the barbiturates are CNS depressants, and simple additive CNS depression provides part of the explanation. Acute alcohol ingestion may inhibit the liver enzymes concerned with the metabolism of barbiturates such as phenobarbital and pentobarbital, but chronic exposure to alcohol increases hepatic microsomal enzyme activity and may reduce sedation from barbiturates in patients without liver impairment. - Similarly, chronic exposure to a barbiturate such as phenobarbital may increase alcohol metabolism due to enzyme induction and consequently reduce blood-alcohol levels. ... 

The suggested reasons for this reaction are unknown, but it may possibly be due to several factors. These include enzyme induction by the alcohol, which could possibly increase the metabolism and clearance of cyproterone inereased sexual drive eaused by alcohol, which might oppose the ef-feets of eyproterone and reduced compliance by alcoholic patients who forget to take their tablets while drinking to excess. ... 

Hepatic depletion of vitamin A stores is caused by chronic ethanol consumption (Bonjour, 1981). Night blindness suffered by alcoholics has been attributed to a low intake of vitamin A (McClain et aL, 1979). However, Sato and Lieber (1982) have demonstrated that ethanol depletes hepatic vitamin A stores in baboons and rats even when it is administered in combination with a nutritionally adequate diet. In addition, animals consuming ethanol in marginal diets were depleted more rapidly of vitamin A. No effect of ethanol intake on retinol binding protein or on serum vitamin A levels could be detected in these studies. Leo and Lieber (1982) found that hepatic vitamin A was depleted to one-fifth of normal levels in alcoholics with only moderate liver disease. Sato and Lieber (1982) observed that retinoic acid was more rapidly metabolized by the MFO system after chronic ethanol intake, and they postulated that vitamin A depletion was the result of MFO enzyme induction. 

---